rs17744121

Variant names:

• chr21-29341277-A-G
• rs17744121
• NM_001186.4:c.1777-1122A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001186.4(BACH1):​c.1777-1122A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0344 in 152,346 control chromosomes in the GnomAD database, including 121 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.034 (121 hom., cov: 32)
• Consequence: BACH1 NM_001186.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.542
• Publications: 10 publications found

Genes affected

BACH1 (HGNC:935): (BTB domain and CNC homolog 1) This gene encodes a transcription factor that belongs to the cap'n'collar type of basic region leucine zipper factor family (CNC-bZip). The encoded protein contains broad complex, tramtrack, bric-a-brac/poxvirus and zinc finger (BTB/POZ) domains, which is atypical of CNC-bZip family members. These BTB/POZ domains facilitate protein-protein interactions and formation of homo- and/or hetero-oligomers. When this encoded protein forms a heterodimer with MafK, it functions as a repressor of Maf recognition element (MARE) and transcription is repressed. Multiple alternatively spliced transcript variants have been identified for this gene. [provided by RefSeq, May 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BACH1	NM_001186.4	c.1777-1122A>G		intron_variant	Intron 4 of 4	ENST00000286800.8	NP_001177.1
BACH1	NM_206866.3	c.1777-1122A>G		intron_variant	Intron 4 of 4		NP_996749.1
BACH1	NR_027655.3	n.1956-10357A>G		intron_variant	Intron 4 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BACH1	ENST00000286800.8	c.1777-1122A>G		intron_variant	Intron 4 of 4	1	NM_001186.4	ENSP00000286800.3
BACH1	ENST00000399921.5	c.1777-1122A>G		intron_variant	Intron 4 of 4	1		ENSP00000382805.1
BACH1	ENST00000422809.5	c.471+11584A>G		intron_variant	Intron 2 of 4	5		ENSP00000416569.1
BACH1	ENST00000468059.1	c.324+11584A>G		intron_variant	Intron 2 of 3	3		ENSP00000470673.1

Frequencies

GnomAD3 genomes AF: 0.0345 AC: 5245 AN: 152228 Hom.: 121 Cov.: 32

Gnomad AFR AF: 0.0106

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0270

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0174

Gnomad FIN AF: 0.0404

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0554

Gnomad OTH AF: 0.0306

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0344 AC: 5248 AN: 152346 Hom.: 121 Cov.: 32 AF XY: 0.0322 AC XY: 2399 AN XY: 74500

African (AFR) AF: 0.0106 AC: 439 AN: 41594

American (AMR) AF: 0.0269 AC: 412 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0115 AC: 40 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5190

South Asian (SAS) AF: 0.0182 AC: 88 AN: 4834

European-Finnish (FIN) AF: 0.0404 AC: 429 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0554 AC: 3768 AN: 68036

Other (OTH) AF: 0.0303 AC: 64 AN: 2114

Alfa AF: 0.0478 Hom.: 540

Bravo AF: 0.0320

Asia WGS AF: 0.00664 AC: 24 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.6
DANN	Benign	0.64
PhyloP100		0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17744121; hg19: chr21-30713598;